Expert Explainer: Why is a cure for HIV so difficult? – Schulich School of Medicine and Dentistry

jessica prodgerA professor in the Department of Microbiology and Immunology, he is researching ways to prevent HIV infection and why certain individuals are more susceptible to the virus to combat the epidemic in sub-Saharan Africa. Professor of Microbiology and Immunology jimmy dikeakos and postdoctoral fellow mitchell mumby We study different parts of the HIV virus and how viral proteins control immune responses in infected people. They spoke about progress towards achieving UNAIDS' goals and why a cure for HIV remains so difficult.

Schulich News: What is HIV?

Jimmy Dikeacos (JD): Although HIV is a very small and simple virus, it is also a very complex virus. When expressed in infected cells, it can trick the immune system into not recognizing its presence. HIV is a retrovirus and is difficult to treat because it is a latent infection. If left untreated, it can lead to AIDS.

Jessica Prodger (Japan): This virus infects the cells that provide us with immunological memory. These cells are some of the same cells that contribute to the lifelong protection caused by childhood vaccinations.

Why is HIV so difficult to treat?

day: HIV is difficult to treat because part of the virus's life cycle involves integrating its own DNA into the human DNA of the cells it infects. These cells are very long-lived and can remain dormant for long periods of time. As a result, the HIV DNA in the body also becomes dormant. When these cells become reactivated, the HIV DNA within them can produce new viruses that can be released from the cells and infect new cells or infect other people. However, while cells are dormant, our immune system cannot detect HIV DNA hidden in latent reservoirs.

Currently, the drugs available to treat HIV only prevent new infections from occurring and have no effect on the HIV DNA that is hidden within a person's DNA. Additionally, while our bodies have many safeguards against DNA damage and mutations, there is no natural system to seek out and excise non-human DNA.

Eliminating or permanently silencing this HIV DNA, or the cells that carry it, is a challenge for HIV treatment research.

What current treatments are available to help people living with HIV?

JD: A group of drugs called antiretroviral therapy (ART) inhibit stages of the virus's life cycle. These block the function of an enzyme called reverse transcriptase or integrase. This treatment can stop most viruses from replicating, helping individuals live healthier lives.

Mitchell Manby (MM): In recent years, ART has shown significant promise as a preventive measure through pre-exposure prophylaxis (PrEP). People at risk for HIV infection can take PrEP, and if adherence is maintained, HIV infection becomes very rare. However, traditional PrEP formulations require daily pills, making long-term compliance difficult and increasing the likelihood of HIV infection.

A recent study tested a new treatment called lenacapavir, injected twice a year, among young women in South Africa and Uganda, resulting in zero HIV infections. This innovation has the potential to significantly improve PrEP adherence and reduce infection rates.

The pressing challenge is to ensure access to this innovative PrEP regimen in regions and communities around the world where HIV infection remains endemic.

How much progress is being made toward eliminating HIV and AIDS as a public health concern?

JD: Globally, we have made great progress over the past few decades. There are currently more than 25 ARTs available to people living with HIV. There has been a large-scale education effort to encourage individuals to get tested. Unfortunately, there is still a lot of stigma around HIV in some parts of the world, and even in Canada, and not everyone wants to get tested to take advantage of these treatment strategies. There is still a long way to go in terms of education so that everyone understands that people living with HIV can live better lives when they are treated.

What needs to be done to achieve the 95-95-95 goals by 2030?

MM: Achieving these goals is a sociocultural and economic challenge rather than a virological one. Achieving the 95-95-95 goal by 2030 will require significant and sustained investment in testing and access to ART, both in the treatment of people living with HIV and in prevention with PrEP.

HIV disproportionately affects key populations around the world, including men who have sex with men, intravenous drug users, sex workers, adolescent girls, and young women. At-risk groups may avoid seeking care because they fear discrimination or even imprisonment in places with strict laws prohibiting homosexuality, sex work, and drug use. Because ART is required throughout life, cumulative lifetime costs are significant at both the individual and population level, making programs to ensure access to ART essential, especially in low- and middle-income countries.

Achieving the 95-95-95 goals will require widespread education and testing programs and the integration of HIV care into existing health infrastructure.

JD: Some of the biggest hurdles are not only strengthening and developing treatment strategies, but also ensuring that all infected people know they are infected. We need to remain hopeful and optimistic. It is important to work towards these goals and the goal of ending the epidemic.